This application seeks support for a broad program of research directed toward understanding of cardiovascular and metabolic aspects of electrolyte transport. Investigations will focus (1) on the molecular mechanisms determining and controlling passive and active transport steps across individual cell membranes and across epithelia, (2) on the relationship between transport and metabolism, and (3) on the electrical manifestations of ion transport. The nature of membrane transport defects in some diseases and disease models will also be studied. Experiments will be carried out on single cells (red blood cells, bacteria), isolated epithelia (renal tubule, intestinal mucosa, frog skin, Amphiuma bladder) and on organ systems (Kidney, heart, intestine). A broad spectrum of approaches will be used, including measurements of transport rates, tracer fluxes, fluorescence and electrical properties. A special effort will be made by the use of electronmicroscopic and autoradiographic methods to gain new information on fine structural correlates of ion and fluid transport.